Visceral ischemia-reperfusion injury promotes tumor necrosis factor (TNF) and interleukin-1 (IL-1) dependent organ injury in the mouse

Acute visceral ischemia and subsequent reperfusion injury, which accompanies the surgical repair of a thoracoabdominal aorta aneurysm, is associated with high rates of morbidity and mortality. The purpose of the present study was to determine whether endogenous tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) production contributes to organ dysfunction in animals subjected to viscera! ischemia secondary to 30 min of supraceliac aortic occlusion. C57BL6/j mice were treated with either a TNF binding protein (TNF-bp-10 mg/kg) or an anti-IL-1 receptor type 1 antibody (150 μg) 2 h prior to 30 min of supraceliac aortic occlusion. An additional group of mice received 30 min of infrarenal aortic occlusion to determine the contribution of lower torso ischemia-reperfusion injury to the changes seen following supraceliac aortic occlusion. Visceral organ ischemia for 30 min produced by supraceliac aortic occlusion followed by 2 h of reperfusion produced measurable TNF-α in 38% of untreated mice, but TNF-α was undetectable in both sham-operated mice and following infrarenal aortic occlusion. After 2 h of reperfusion, lung myeloperoxidase levels were significantly elevated in the mice experiencing visceral ischemia-reperfusion compared with either a sham operation or infrarenal ischemia-reperfusion (11.6 ± 1.3 U/g vs. 3.4 ±.2 U/g and 3.7 ± 1.0 U/g, respectively, p < .05). Pretreatment with TNF-bp and anti-IL-1 antibody decreased lung neutrophil recruitment (7.2 ± 1.2 U/g and 4.6 ± 1.1 U/g) and capillary membrane permeability changes in mice following visceral ischemia-reperfusion. The present study demonstrates that brief (30 min) clinically relevant visceral ischemia produces TNF-α and IL-1 dependent lung injury.